The capacity of cells and animals to sense and adapt to fluctuations in the availability of energetic substrates is commonly described as metabolic flexibility. This flexibility allows for example the transition from fed to fasting states and to meet the energy demands of exercise in both states. Flexibility is disrupted in pathological conditions such as the metabolic syndrome but in contrast, it is enhanced in some tumours. Lipid droplets (LDs) and mitochondria are key organelles in bioenergetics. In all eukaryotic cells, LDs store and supply essential lipids to produce signalling molecules, membrane building blocks, and the metabolic energy needed to survive during nutrient poor periods. Highly conserved, robust, and regulated mechanisms ensure these bioenergetic fluxes. Although mitochondria are recognized as the epicentre of metabolic flexibility, the contribution of LDs and LD-proteins is often neglected or considered detrimental. Here, we revisit the key roles of LDs during fasting and the intimate collaboration existing with mitochondria when cells sense and respond to fluctuations in substrate availability.

细胞和动物感知和适应能量底物可用性波动的能力通常被描述为代谢灵活性。这种灵活性允许例如从进食状态过渡到禁食状态，并满足两种状态下运动的能量需求。灵活性在代谢综合征等病理条件下被破坏，但相反，它在某些肿瘤中得到增强。脂滴 (LD) 和线粒体是生物能量学中的关键细胞器。在所有真核细胞中，LDs 储存和供应必需的脂质，以产生信号分子、膜构建块和在营养缺乏时期生存所需的代谢能量。高度保守、稳健和受监管的机制确保了这些生物能通量。尽管线粒体被认为是代谢灵活性的中心，但 LD 和 LD 蛋白的贡献往往被忽视或被认为是有害的。在这里，我们重新审视了禁食期间 LDs 的关键作用，以及当细胞感知和响应底物可用性波动时与线粒体存在的密切合作。